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Intra-axonal virus in demyelinative lesions of experimental herpes simplex type 2 infection
Abstract:
Three-week-old mice which had been infected intracerebrally with herpes simplex virus type 2 (HSV-2) were examined electron-microscopically for the presence of intra-axonal virus in or near optic nerve and spinal cord demyelinative lesions. Acute lesions and their margins frequently contained a very small proportion of abnormal axons, and in a few of these mature virus particles, nucleocapsids, or other incomplete forms were found. A similar range of particle morphology was present in the cytoplasm of infected and degenerating glia. Axons containing similar particles were not identified in fibers in normal white matter surrounding demyelinative lesions. It is proposed that neuronal infection and axonal transport of virus may lead to foci of oligodendroglial infection, destruction and central nervous system (CNS) demyelination near to or remote from the cell bodies of infected neurons. In some instances, the topography of lesions could reflect a tract association. Anatomical features of nervous tissue could favor amplification of demyelination from a relatively minimal neuronal infection, with little evidence of tract degeneration. This hypothesis is consistent with the great predominance of demyelination relative to gray matter disease seen experimentally in non-fatal CNS infections with HSV-2. It would also explain the marked tendency for demyelinative lesions in at least certain CNS locations to be greatly elongated in the long axis of fiber tracts. This mechanism could be of importance in other animal models of virus-induced demyelination, and perhaps also in multiple sclerosis.
Insights
Herpes simplex virus type 2 (HSV-2) infection in mice suggests neuronal transport of the virus can cause central nervous system (CNS) demyelination. This may explain lesion patterns in HSV-2 infections and potentially multiple sclerosis.
Area of Science:
- Neurovirology
- Immunology
- Pathology
Background:
- Herpes simplex virus type 2 (HSV-2) can cause central nervous system (CNS) infections.
- Understanding the mechanisms of HSV-2-induced demyelination is crucial for developing effective treatments.
- Previous studies have focused on direct glial infection, but the role of neuronal infection remains less clear.
Purpose of the Study:
- To investigate the presence and role of intra-axonal herpes simplex virus type 2 (HSV-2) in demyelinative lesions within the CNS of infected mice.
- To explore the hypothesis that neuronal infection and axonal transport of HSV-2 contribute to oligodendroglial infection and subsequent demyelination.
Main Methods:
- Electron microscopy was used to examine optic nerve and spinal cord tissues from three-week-old mice infected intracerebrally with HSV-2.
- The study focused on identifying viral particles within axons, particularly in and around demyelinative lesions.
Main Results:
- Abnormal axons containing mature virus particles, nucleocapsids, or incomplete forms were found in acute lesions and their margins.
- Similar viral particle morphology was observed in the cytoplasm of infected and degenerating glia.
- Axons with viral particles were not detected in normal white matter adjacent to lesions.
Conclusions:
- Neuronal infection and axonal transport of HSV-2 are proposed mechanisms leading to oligodendroglial infection and CNS demyelination.
- This pathway may explain the characteristic elongated shape and tract association of demyelinative lesions observed in HSV-2 infections.
- The findings suggest a potential role for this mechanism in other viral demyelination models and possibly in multiple sclerosis pathogenesis.